In this award from the Chemistry of Life Processes Program in the Chemistry Division, Dr. Igor Lednev, from the University at Albany, SUNY, New York, will study the mechanism of refolding of fibrils, which are protein aggregates with a common cross-beta sheet structure. It is well accepted that fibrils are extraordinarily stable and are the most energetically favorable forms of proteins.
The main objectives of the proposed research are: (i) to establish the kinetic mechanism of spontaneous refolding of apo-alpha-lactalbumin fibrils by a combination of modern spectroscopic techniques, including deep ultraviolet Raman spectroscopy, intrinsic fluorescence, atomic force microscopy, and scanning transmission electron microscopy, with advanced statistical analyses, such as chemometrics and 2D correlation spectroscopy, and (ii) to create a comprehensive map of the accessible pathways of the refolding process by varying the solution temperature, salinity and pH.
The spontaneous refolding of fibrils is relevant to disease, but, more importantly, it is fundamentally significant for biology in general. Understanding the mechanism of this process could allow control of the biological activity of fibrils.
The proposed program trains both graduate and undergraduate students in advanced methods and techniques. This cross-disciplinary project engages students in biophysics, biochemistry and molecular biology, and provides future professional scientists and engineers with a range of important technical skills. Undergraduate and graduate students from historically underrepresented groups (African-American and Latino students) will be engaged in studies related to the proposed work. Research results acquired through this award will be integrated into undergraduate and graduate courses, including Analytical Chemistry, Instrumental Analysis and Theory and Techniques of Biophysics and Biophysical Chemistry.
